Brazilian Journal of Anesthesiology
https://bjan-sba.org/article/doi/10.1016/j.bjane.2013.06.002
Brazilian Journal of Anesthesiology
Scientific Article

Comparison of the effects of dexmedetomidine administered at two different times on renal ischemia/reperfusion injury in rats

Comparação dos efeitos de dexmedetomidina administrada em dois momentos diferentes para lesão de isquemia/reperfusão renal em ratos

Edip Gonullu; Sevda Ozkardesler; Tuncay Kume; Leyla Seden Duru; Mert Akan; Mehmet Ensari Guneli; Bekir Ugur Ergur; Reci Meseri; Oytun Dora

Downloads: 0
Views: 640

Abstract

Background and objectives: We investigated the effect of dexmedetomidine on ischemic renal failure in rats. Methods: In the present study, 26 male adult Wistar albino rats weighting 230-300 g were randomly separated into four groups: sham-operated (n = 5), ischemia reperfusion (IR) (IR group, n = 7), IR/reperfusion treatment with dexmedetomidine (Dex. R group, n = 7) and IR/pre-ischemic treatment with dexmedetomidine (Dex. I group, n = 7). In the first group, sham operation was achieved and renal clamps were not applied. For the IR group, renal ischemia was induced by occlusion of the bilateral renal arteries and veins for 60 min followed by reperfusion for 24 h. For the Dex. R and Dex. I groups, the same surgical procedure as in the IR group was performed, and dexmedetomidine (100 mcg/kg intraperitoneal) was administrated at the 5th min after reperfusion and before ischemia. At the end of reperfusion, blood samples were drawn, the rats were sacrificed, and the left kidney was processed for histopathology. Results: The blood urea nitrogen (BUN) levels in groups Dex. R and Dex. I were significantly lower than in the IR group (p = 0.015, p = 0.043), although urine flow was significantly higher in group Dex. R (p = 0.003). The renal histopathological score in the IR group was significantly higher than in the other groups. There was no significant difference between the Dex. R and Dex. I groups. Conclusions: The results were shown that administration of dexmedetomidine reduced the renal IR injury histomorphologically. Administration of dexmedetomidine in the reperfusion period was considered as more effective due to increase in urinary output and decrease in BUN levels.

Keywords

Kidney, Ischemia/reperfusion, Dexmedetomidine, Acute renal failure

Resumo

Justificativa e objetivos: Investigar os efeitos de dexmedetomidina sobre a insuficiência renal isquêmica em ratos. Métodos: No presente estudo, 26 ratos machos adultos, albinos Wistar, com peso 230-300 g, foram randomicamente divididos em quatro grupos: pseudo-operado (n = 5), isquemia-reperfusão (grupo IR, n = 7), IR/tratamento de reperfusão com dexmedetomidina (grupo Dex-R, n = 7) e IR/tratamento pré-isquemia com dexmedetomidina (grupo Dex-I, n = 7). No primeiro grupo, uma pseudo-operação foi feita e clampeamentos renais não foram aplicados. No grupo IR, isquemia renal foi induzida por oclusão das artérias e veias renais bilaterais durante 60minutos seguida por reperfusão durante 24horas. Nos grupos Dex-R e Dex-I, o mesmo procedimento cirúrgico destinado ao grupo IR foi feito e dexmedetomidina (100mcg/kg intraperitoneal) foi administrada cinco minutos após a reperfusão e antes da isquemia. No fim da reperfusão, amostras de sangue foram coletadas, os ratos foram sacrificados e os rins esquerdos processado para histologia. Resultados: Os níveis de nitrogênio ureico no sangue (BUN) dos grupos Dex-R e Dex-I estavam significativamente mais baixos do que os do grupo IR (p = 0,015, p = 0,043), embora o fluxo urinário tenha sido significativamente maior no grupo Dex-R (p = 0,003). O escore histopatológico renal do grupo IR foi significativamente maior do que os dos outros grupos. Não houve diferença significativa entre os grupos Dex-R e Dex-I. Conclusões: Os resultados demonstraram que a administração de dexmedetomidina reduziu histomorfologicamente a lesão de IR renal. A administração de dexmedetomidina durante o período de reperfusão foi considerada como mais eficaz por causa do aumento do débito urinário e da diminuição dos níveis de BUN.

Palavras-chave

Renal, Isquemia/reperfusão, Dexmedetomidina, Insuficiência renal aguda

References

Thadhani R, Pascual M, Bonventre JV. Acute renal failure. N Engl J Med. ;334:1460-1448.

Brezis M, Rosen S, Silva P. Renal ischemia: a new perspective. Kidney Int. ;26:383-375.

Caron A, Desrosiers RR, Béliveau R. Kidney ischemia reperfusion regulates expression and distribution of tubulin subunits, beta-actin and rho GTPases in proximal tubules. Arch Biochem Biophys. ;431:46-31.

Granger DN, Korthuis RJ. Physiologic mechanisms of postischemic tissue injury. Annu Rev Physiol. ;57:311-332.

Brezis M, Rosen S. Hypoxia of the renal medulla-its implications for disease. N Engl J Med. ;332:655-647.

Chiao H, Kohda Y, McLeroy P. Alpha-melanocytestimulating hormone protects against renal injury after ischemia in mice and rats. J Clin Invest. ;99:1165-1172.

Williams P, Lopez H, Britt D. Characterization of renal ischemia-reperfusion injury in rats. J Pharmacol Toxicol Methods. ;37:1-7.

Billings FT, Chen SW, Kim M. Alpha-2 adrenergic agonists protect against radiocontrast-induced nephropathy in mice. Am J Physiol Renal Physiol. ;295:748-741.

Wikberg JE, Uhlén S, Chhajlani V. Medetomidine stereoisomers delineate two closely related subtypes of idazoxan (imidazoline) I-receptors in the guinea pig. Eur J Pharmacol. ;193:335-400.

Scheinin M, Kallio A, Koulu M. Sedative and cardiovascular effects of medetomidine, a novel seletive alpha2-adrenoceptor agonist, in healthy volunteers. Br J Clin Pharmacol. ;24:443-451.

Kallio A, Scheinin M, Koulu M. Effects of deksmedetomidine, a seletive alpha 2-adrenoceptor agonist, on hemodynamic control mechanisms. Clin Pharmacol Ther. ;46:33-42.

Aho M, Scheinin M, Lehtinen AM. Intramusculary administered deksmedetomidine attenuates hemodynamic and stress hormone responses to gynecologic laparoscopy. Anesth Analg. ;75:932-939.

Talke P, Chen R, Thomas B. The hemodynamic and adrenergic effects of perioperative deksmedetomidine infusion after vascular surgery. Anesth Analg. ;90:839-834.

Jalonen J, Hynynen M, Kuitunen A. Deksmedetomidine as an anesthetic adjunct in coronary artery bypass grafting. Anesthesiology. ;86:345-331.

Villela NR, do Nascimento P, de Carvalho LR. Effects of dexmedetomidine on renal system and on vasopressin plasma levels. Experimental study in dogs.. Rev Bras Anestesiol. ;55:429-440.

Frumento RJ, Logginidou HG, Wahlander S. Deksmedetomidine infusion is associated with enhanced renal function after thoracic surgery. J Clin Anesth. ;18:422-426.

Kocoglu H, Ozturk H, Ozturk H. Effect of deksmedetomidine on ischemia-reperfusion injury in rat kidney a histopathologic study. Renal Failure. ;31:74-70.

Feng L, Xiong Y, Cheng F. Effect of ligustrazine on ischemia-reperfusion injury in murine kidney. Transplant Proc. ;36:1949-1951.

Fujii T, Takaoka M, Muraoka T. Preventive effect of lcarnosine on ischemia/reperfusion-induced acute renal failure in rats. Eur J Pharmacol. ;474:261-267.

Hull ME. A new doctor for a men diabetes and hypertension;. Tietz's applied laboratory medicine. :74-65.

Hussein Ael-A, Shokeir AA, Sarhan ME. Effects of combined erythropoietin and epidermal growth factor on renal ischaemia/reperfusion injury: a randomized experimental controlled study. BJU Int. ;107:323-328.

Gu J, Sun P, Zhao H. Dexmedetomidine provides renoprotection against ischemia-reperfusion injury in mice. Crit Care. ;15:153.

Yamamoto K, Wilson DR, Baumal R. Outer medullary circulatory defect in ischemic acute renal failure. Am J Pathol. ;116:253-261.

Arendshorst WJ, Finn WF, Gottschalk CW. Pathogenesis of acute renal failure following temporary renal ischemia in the rat. Circ Res. ;37:568-558.

Bird JE, Milhoan K, Wilson CB. Ischemic acute renal failure and antioxidant therapy in the rat: the relation between glomerular and tubular dysfunction. J Clin Invest. ;81:1630-1638.

Weinberg JM. The cell biology of ischemic renal injury. Kidney Int. ;39:476-500.

Hoffman WE, Kochs E, Werner C. Deksmedetomidine improves neurologic outcome from incomplete ischemia in the rat. Reversal by the alpha 2-adrenergic antagonist atipamezole.. Anesthesiology. ;75:328-332.

Maier CM, Sun GH, Kunis DM. Neuroprotection by the N- methyl- d- aspartate receptor antagonist CGP 40116: In vivo and in vitro studies. J Neurochem. ;65:652-659.

Koçŏglu H, Karaaslan K, Gonca E. Preconditioning effects of dexmedetomidine on myocardial ischemia/reperfusion injury in rats. Curr Ther Res. ;69:150-158.

Simonson SG, Zhang J, Canada AT. Hydrogen peroxide production by monoamine oxidase during ischemia-reperfusion in the rat brain. J Cereb Blood Flow Metab. ;13:125-134.

Suzuki T, Akaike N, Ueno K. MAO inhibitors, clorgyline and lazabemide, prevent hydroxyl radical generation caused by brain ischemiarreperfusion in mice. Pharmacology. ;50:357-362.

Engelhard K, Werner C, Eberspächer E. The effect of the alpha 2-agonist deksmedetomidine and the N-methyl- d- aspartate antagonist S(+)-ketamine on the expression of apoptosis regulating proteins after incomplete cerebral ischemia and reperfusion in rats. Anesth Analg. ;96:524-531.

Wijeysundera DN, Naik JS, Beattie WS. Alpha-2 adrenergic agonists to prevent perioperative cardiovascular complications: a meta-analysis. Am J Med. ;114:752-742.

Hoffman WE, Baughman VL, Albrecht RF. Interaction of catecholamines and nitrous oxide ventilation during incomplete brain ischemia in rats. Anesth Analg. ;77:908-912.

Curtis FG, Vianna PT, Viero RM. Dexmedetomidine and S(+)-ketamine in ischemia and reperfusion injury in the rat kidney. Acta Cir Bras. ;26:202-206.

Yuzer H, Yuzbasioglu MF, Ciralik H. Effects of intravenous anesthetics on renal ischemia/reperfusion injury. Renal Failure. ;31:296-290.

Rusafa E, Vianna PT, Viero RM. Influence of S(+)-ketamine analgesia in renal intraoperative ischemia. Histological study in rats.. Acta Cir Bras. ;21:246-242.

Lee HT, Ota-Setlik A, Fu Y. Differential protective effects of volatile anesthetics against renal ischemia-reperfusion injury in vivo. Anesthesiology. ;101:1313-1324.

5dcda2fb0e88257105bf58f1 rba Articles
Links & Downloads

Braz J Anesthesiol

Share this page
Page Sections